NF1 mice also had more robust dopaminergic and behavioral responses to salient visual stimuli, which were independent of learning, and rescued by optogenetic inhibition of non-dopaminergic neurons in the VTA. We found that NF1 mice exhibit reduced spontaneous dopaminergic neurotransmission that was associated with excitation/inhibition imbalance in the ventral tegmental area and abnormal neuronal morphology. Additionally, we developed novel systemic AAV vectors to facilitate morphological reconstruction of dopaminergic populations in cleared tissue. We employed the genetically encoded optical dopamine sensor dLight1 to monitor dopaminergic neurotransmission in the ventral striatum of NF1 mice during motivated behavior. However, these circuits have never been directly assayed in vivo. Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder whose neurodevelopmental symptoms include impaired executive function, attention, and spatial learning and could be due to perturbed mesolimbic dopaminergic circuitry.

Graphpad prism 8 trial